New tests appear to substantiate findings of heart-valve abnormalities in about a third of the people who took the diet drugs Redux and Pondimin --even as American Home Products Corp. steps up its investigation of the validity of earlier data that led to the drugs' recall.
The new findings forwarded to the Food and Drug Administration involve several hundred more patients. But they aren't very likely to end debate over the validity of the original research behind the recall. Nor will they resolve questions about the extent of the danger the medicines pose for the 70 million people around the world who took them.
American Home, which sold the drugs domestically, is working aggressively to obtain the raw patient data being reviewed by the FDA, in an apparent attempt to build its defenses against a rash of lawsuits that have been filed against it.
The company, which all along has expressed skepticism that the drugs cause heart-valve problems, has asked the FDA to release the raw data -- including actual videotapes of the sonic electrocardiogram images of patients' hearts.
But the FDA has refused, saying that the data belong to the doctors who sent it in. "It's not our information to give," says David Graham, the FDA's acting chief of epidemiology.
On Sept. 15, the FDA requested that the drugs be recalled, based on data showing that 92 of 291 people who took Redux or Pondimin -- a surprisingly high 32% -- had leaky heart valves, a potentially life-shortening condition.
The initial echocardiogram results came from four doctors and a nurse who had responded to an FDA request for information after the first valve problems were reported in July by the Mayo Clinic. The most recent data were forwarded to the FDA by these same five medical professionals.
"Based on all the data we've received subsequently, we think that the 32% estimate is a very solid number," says the FDA's Dr. Graham. He concedes its sample wasn't scientifically selected, but says "there's less than a one-in-a-million chance that the results in our survey could have occurred by chance."
American Home has contacted the doctors in its own attempt to get the raw data. Marc Deitch, global medical director for the company's Wyeth-Ayerst Laboratories unit, says the company wants to "do a thorough evaluation" of the data, including having the echocardiogram results reviewed by people who don't know the history of the patient in question. That's necessary, Dr. Deitch says, because "there is a degree of subjectivity in the reading of an echocardiogram." American Home also says it believes the incidence of valve problems in the general population may be greater that the FDA is assuming.
Three of the medical centers say they have either given American Home the raw data or plan to -- but two have refused. "I'm not giving data to anyone except the FDA," says Susan Rasmussen, a clinical nurse specialist at Hendricks Community Hospital, in Danville, Ind.
Ms. Rasmussen, who runs a screening program for diet-drug users at the hospital, says the initial FDA report used the first 30 patients she tested. Including the original 30, she says, "I've done well over 100, and we're finding a very solid representation of abnormalities." In her total sample, both new and old, about 35% to 38% of patients showed leaky heart valves on the imaging tests.
The FDA declines to say how many more echocardiograms it has reviewed, but Richard Bowen, a diet doctor in Naples, Fla., says he has sent in at least an additional 60 since forwarding an original 122 tests to the FDA. The second batch shows results similar to the earlier sample, he says.
Mehmood Khan, head of the department of endocrinology and nutrition at Hennepin County Medical Center in Minneapolis, also contributed samples used in the first FDA report. He says he's now got "hundreds" of additional echocardiograms that uphold earlier findings. "I'm not at liberty to share the data," Dr. Khan says, "but there is absolutely no reason to change what has been done."
With funding from the National Institutes of Health, Dr. Khan is now giving echocardiograms to overweight patients who have not taken diet drugs. This will provide a control-group comparison that scientists say is much needed. Analyzing the results will take up to two months, he says.
Precise figures on the incidence of leaky valves in people who haven't taken diet drugs are hard to come by, but a number of cardiologists estimate a range of about 1% to 5%.
Dr. Khan is also testing people who have lost weight after taking the radical step of having their stomachs stapled. This might clear up potential questions over whether the heart-valve abnormalities could have been caused by the rapid weight loss, not the drugs themselves. "The panic has occurred based on nonscientific data," he says. "We plan to do carefully controlled research."
Reports of large numbers of unaffected patients have also begun to surface. T. Anthony Don Michael, a Bakersfield, Calif., cardiologist, says none of about 70 of his patients on diet drugs developed new heart-valve problems in echocardiograms he ordered. Two or three of the patients had prior problems, which didn't change.
"We didn't find any heart-valve problems that weren't there before," says Dr. Don Michael, who had given all his patients echocardiograms prior to beginning diet drugs because all were trying to lose weight to improve the condition of their hearts.
Dr. Don Michael, who hasn't yet submitted these results to the FDA but plans to, says he doesn't know why his data appear to contradict the agency's. But his patients were on the drugs for short periods of time -- never more than six months. Patients in the FDA sample had taken the drugs an average of one year.
Although numerous unanswered questions remain, Dr. Susan Yanovsky, director of the NIH's obesity program, says she believes the FDA made the right decision. "When the public health is at stake," she says, "we don't have the luxury of time."
The FDA's Dr. Graham says he has heard -- but not verified -- three reports of patients whose heart-valve problems appeared to reverse themselves once they stopped taking the drugs. He also has heard several other reports of patients whose disease remained.
Jack L. Crary, a cardiologist at MeritCare Medical Center in Fargo, N.D., and co-author of a New England Journal of Medicine article that broke the news that the drugs might cause heart problems, says his experience so far is that the trouble clears up. But for how long?
"Moderate, even severe cases seem to improve or reverse themselves -- so I'm very hopeful," he says. "The bigger question is what's going to happen in five, 10 or 15 years. If these valves are mildly damaged, will they develop problems later? We just don't know."
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